A novel approach demonstrated durable responses in the treatment of patients with smoldering multiple myeloma (SMM), according to phase II trial results presented at the 2017 ASH Annual Meeting.

A prior phase III study, conducted by the Spanish Myeloma Group, showed that treatment with lenalidomide (Revlimid) and dexamethasone early in a treatment course for patients with SMM, an asymptomatic plasma cell disorder that includes patients with a different risk for progression to multiple myelomas, may significantly improve progression-free survival (PFS).

“This curative approach for high-risk SMM seems to be encouraging,” said Maria-Victoria Mateos, MD, PhD, University Hospital of Salamanca in Spain. She presented results from a single-arm, phase II trial during an oral abstract session Sunday.

The single-arm, phase II trial evaluated a strategy using induction therapy with carfilzomib (Kyprolis), lenalidomide, and dexamethasone followed by high-dose therapy and autologous stem cell transplantation (HDT-ASCT), consolidation therapy and then maintenance therapy with lenalidomide and dexamethasone.

Ninety patients (median age, 59 years) were recruited from June 2015 to June 2017. All patients were at high risk for progression, defined as having a risk of 50% or more at 2 years, according to Mayo (n = 19), Spanish (n = 47) or both (n = 24) risk models.

Next, 35 patients received two consolidation cycles of carfilzomib, lenalidomide and dexamethasone. Twenty-nine of those patients went to receive maintenance therapy with 10 mg lenalidomide on days 1 through 21, plus 20 mg dexamethasone weekly for up to 2 years.

All 42 patients achieved an overall response following HDT-ASCT including 22 stringent CRs (52%), 2 CRs (5%), 12 VGPRs (29%), and 6 PRs (14%). Half of those patients were MRD-negative, an improvement of 47% in the quality of response over treatment. Peripheral blood stem cell collection was successful in all but 1 patient, with a median number of CD34+ cells collected of 6.79 x 106/Kg. Engraftment occurred in all patients, and the median number of CD34+ infused was 3.29 x 106/Kg. No patient discontinued during treatment or in the 100 days post-HDT-ASCT.

All patients who completed the 2 planned consolidation cycles had an overall response, including 24 stringent CRs (69%), 2 CRs (6%), 7 VGPRs (20%), and 2 PRs (6%). Sixty percent of these patients were MRD-negative, an improvement of 62% in the quality of response over treatment. No patients discontinued consolidation. During consolidation, 2 patients developed grade 3/4 neutropenia.